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Senescence plays a key role in various physiological and pathological processes. We reported that injury-induced transient senescence correlates with heart regeneration, yet the multi-omics profile and molecular underpinnings of regenerative senescence remain obscure. Using proteomics and single-cell RNA sequencing, here we report the regenerative senescence multi-omic signature in the adult mouse heart and establish its role in neonatal heart regeneration and agrin-mediated cardiac repair in adult mice. We identified early growth response protein 1 (Egr1) as a regulator of regenerative senescence in both models. In the neonatal heart, Egr1 facilitates angiogenesis and cardiomyocyte proliferation. In adult hearts, agrin-induced senescence and repair require Egr1, activated by the integrin-FAK-ERK-Akt1 axis in cardiac fibroblasts. We also identified cathepsins as injury-induced senescence-associated secretory phenotype components that promote extracellular matrix degradation and potentially assist in reducing fibrosis. Altogether, we uncovered the molecular signature and functional benefits of regenerative senescence during heart regeneration, with Egr1 orchestrating the process.
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Proliferación Celular , Senescencia Celular , Proteína 1 de la Respuesta de Crecimiento Precoz , Miocitos Cardíacos , Regeneración , Animales , Proteína 1 de la Respuesta de Crecimiento Precoz/metabolismo , Proteína 1 de la Respuesta de Crecimiento Precoz/genética , Regeneración/fisiología , Senescencia Celular/fisiología , Miocitos Cardíacos/metabolismo , Ratones Endogámicos C57BL , Neovascularización Fisiológica/fisiología , Transducción de Señal , Fibroblastos/metabolismo , Ratones , Proteínas Proto-Oncogénicas c-akt/metabolismo , Células Cultivadas , Animales Recién Nacidos , Modelos Animales de Enfermedad , Fenotipo Secretor Asociado a la Senescencia , Proteómica , Análisis de la Célula Individual , Masculino , Quinasas MAP Reguladas por Señal Extracelular/metabolismo , Ratones Noqueados , Quinasa 1 de Adhesión FocalRESUMEN
Objective: Diagnosing tuberculosis (TB) can be particularly challenging in the absence of sputum for pulmonary tuberculosis cases and extrapulmonary TB (EPTB). This study evaluated the utility of nanopore-based targeted next-generation sequencing (tNGS) for diagnosing TB in tissue samples, and compared its efficacy with other established diagnostic methods. Methods: A total of 110 tissue samples from clinical cases were examined. The sensitivity and specificity of tNGS were benchmarked against a range of existing diagnostic approaches including hematoxylin and eosin (HE) staining in conjunction with acid-fast bacilli (AFB) detection, HE staining combined with PCR, HE staining paired with immunohistochemistry (IHC) using anti-MPT64, and the Xpert Mycobacterium tuberculosis (MTB)/rifampicin (RIF) assay. Results: The sensitivity and specificity of tNGS were 88.2 and 94.1%, respectively. The respective sensitivities for HE staining combined with AFB, HE staining combined with PCR, HE staining combined with IHC using anti-MPT64, and Xpert MTB/RIF were 30.1, 49.5, 47.3, and 59.1%. The specificities for these methods were 82.4, 88.2, 94.1, and 94.1%, respectively. Analysis of drug resistance based on tNGS results indicated that 10 of 93 TB patients (10.75%) had potential drug resistance. Conclusion: Targeted next-generation sequencing achieved higher accuracy than other established diagnostic methods, and can play a crucial role in the rapid and accurate diagnosis of TB, including drug-resistant TB.
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Background: In this study, we investigated clinical prediction factors of nonchronic total occlusion lesion (NCTOL) progression in patients who underwent percutaneous coronary intervention (PCI) for chronic total occlusion (CTO) lesions. Methods: In total, 450 patients with unstable angina (mean age = 57.1 ± 9.2 years) who underwent PCI for CTO lesions between January 2016 and December 2018 at Beijing Anzhen Hospital were enrolled in this study. A clinical and angiographic follow-up examination was performed 12 months postoperatively. The patients were divided into NCTOL progression (145 cases) and control (305 cases) groups based on the outcome of the 12-month angiographic follow-up. The clinical and angiographic features of the participants were analyzed. Results: The adenosine diphosphate-induced platelet aggregation (ADP-IPA) rate and levels of lipoprotein (a) (Lp(a)) in the NCTOL progression group were significantly higher than those in the control group (51.89 ± 14.81 vs. 39.63 ± 17.12, P < 0.01; 0.22 ± 0.26 vs. 0.14 ± 0.18, P < 0.05, respectively). Logistic regression showed that the ADP-IPA rate (odds ratio = 1.047, 95 % confidence interval: 1.014-1.082, P = 0.005) and Lp(a) (odds ratio = 11.972, 95 % confidence interval: 1.230-116.570, P = 0.033) were independent predictors of NCTOL progression. Partial correlation analysis demonstrated that the ADP-IPA rate was positively correlated with NCTOL progression (r = 0. 351, P < 0.001). Receiver operating characteristic curve showed that the boundary point of the ADP-IPA rate to predict NCTOL progression was 30 % (sensitivity, 86.2 %; specificity, 68.9 %). Conclusions: NCTOL progression is an important cause of recurrent PCI in patients with coronary artery disease after PCI for CTO lesions. The ADP-IPA rate is a useful predictor for NCTOL progression in patients with unstable angina who undergo PCI for CTO lesions.
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In cases where a client suffers from completely unlabeled data, unsupervised learning has difficulty achieving an accurate fault diagnosis. Semi-supervised federated learning with the ability for interaction between a labeled client and an unlabeled client has been developed to overcome this difficulty. However, the existing semi-supervised federated learning methods may lead to a negative transfer problem since they fail to filter out unreliable model information from the unlabeled client. Therefore, in this study, a dynamic semi-supervised federated learning fault diagnosis method with an attention mechanism (SSFL-ATT) is proposed to prevent the federation model from experiencing negative transfer. A federation strategy driven by an attention mechanism was designed to filter out the unreliable information hidden in the local model. SSFL-ATT can ensure the federation model's performance as well as render the unlabeled client capable of fault classification. In cases where there is an unlabeled client, compared to the existing semi-supervised federated learning methods, SSFL-ATT can achieve increments of 9.06% and 12.53% in fault diagnosis accuracy when datasets provided by Case Western Reserve University and Shanghai Maritime University, respectively, are used for verification.
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The optimized selection method can maximize the genetic gain in offspring under the premise of controlling the inbreeding level of the population. At present, genetic gain has been largely improved by using genomic selection in multiple farm animals. However, the design of the optimal selection method and assessment of its effects during long-term selection in beef cattle breeding are yet to be fully explored. In this study, a simulated beef cattle population was constructed, and 15 generations of simulated breeding were carried out using the linear programming breeding strategy (LP) and optimal contribution selection strategy (OCS), respectively. The truncation selection strategy (TS-I and TS-II) was used as the control. During the breeding process, genetic parameters including genetic gain, average kinship coefficient, QTL effect variance, and average observed heterozygosity were calculated and compared across generations. Our results showed that the LP method can significantly improve the genetic gain in the population, especially the genetic performance of the traits with high heritability and the traits with high weight in the breeding process, but the inbreeding level of the population is higher under LP strategy. Although the genetic gain in the population under the OCS strategy is lower than the TS-II strategy, this method can effectively control the inbreeding level of the population. Our findings also suggest that the LP and OCS method can be used as an effective means to improve genetic gain, while the OCS method is a more ideal method to obtain sustainable genetic gain during long-term selection.
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Federated learning (FL) is an effective method when a single client cannot provide enough samples for multiple condition fault diagnosis of bearings since it can combine the information provided by multiple clients. However, some of the client's working conditions are different; for example, different clients are in different stages of the whole life cycle, and different clients have different loads. At this point, the status of each client is not equal, and the traditional FL approach will lead to some clients' useful information being ignored. The purpose of this paper is to investigate a multiscale recursive FL framework that makes the server more focused on the useful information provided by the clients to ensure the effectiveness of FL. The proposed FL method can build reliable multiple working condition fault diagnosis models due to the increased focus on useful information in the FL process and the full utilization of server information through local multiscale feature fusion. The validity of the proposed method was verified with the Case Western Reserve University benchmark dataset. With less local client training data and complex fault types, the proposed method improves the accuracy of fault diagnosis by 23.21% over the existing FL fault diagnosis.
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BACKGROUND: To investigate the relationship between the clinical features and progression of non-culprit lesions in patients with ST-elevation myocardial infarction (STEMI) after primary percutaneous coronary intervention (PPCI). METHODS: A total of 480 patients (57.1 ± 9.2 y) with STEMI who underwent PPCI between January 2016 and December 2017 in Beijing Anzhen Hospital were enrolled in this study. All patients underwent PPCI as a treatment for culprit lesions. Clinical and angiographic follow-up were performed for 12 months. All patients were divided into a non-culprit lesions (NCL) progression group (205 cases) and a control group (275 cases) based on angiographic follow-up outcomes at 12 months. The clinical and angiographic features were analyzed. RESULTS: Body mass index (BMI), serum creatinine (Scr), fasting blood glucose (FBG), glycated serum albumin, glycated hemoglobin and homocysteine levels in the NCL progression group were significantly higher than those in the control group (P < 0.05). A logistic regression analysis showed that FBG (odds ratio 1.274, 95% confidence interval 1.077-1.505, P = 0.005) and Scr (odds ratio 1.020, 95% confidence interval 1.002-1.038, P = 0.027) were independent predictors of NCL progression. A partial correlation analysis showed that FBG was positively correlated with NCL progression (r = 0.231, P = 0.001). A receiver operating characteristic curve showed that the boundary point of FBG to predict NCL progression was 5.715 mmol/L, and the sensitivity was 74.4% and the specificity was 46.4%. CONCLUSION: FBG is a valuable predictor for NCL progression in patients with STEMI after PPCI.
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Intervención Coronaria Percutánea , Infarto del Miocardio con Elevación del ST , Humanos , Intervención Coronaria Percutánea/efectos adversos , Infarto del Miocardio con Elevación del ST/diagnóstico por imagen , Infarto del Miocardio con Elevación del ST/terapiaRESUMEN
Carcass yield traits are of considerable economic importance for farm animals, which act as a major contributor to the world's food supply. Genome-wide association studies (GWASs) have identified many genetic variants associated with carcass yield traits in beef cattle. However, their functions are not effectively illustrated. In this study, we performed an integrative analysis of gene-based GWAS with expression quantitative trait locus (eQTL) analysis to detect candidate genes for carcass yield traits and validate their effects on bovine skeletal muscle satellite cells (BSCs). The gene-based GWAS and cis-eQTL analysis revealed 1780 GWAS and 1538 cis-expression genes. Among them, we identified 153 shared genes that may play important roles in carcass yield traits. Notably, the identified cis-eQTLs of PON3 and PRIM2 were significantly (p < 0.001) enriched in previous GWAS loci for carcass traits. Furthermore, overexpression of PON3 and PRIM2 promoted the BSCs' proliferation, increased the expression of MYOD and downregulated the expression of MYOG, which indicated that these genes may inhibit myogenic differentiation. In contrast, PON3 and PRIM2 were significantly downregulated during the differentiation of BSCs. These findings suggested that PON3 and PRIM2 may promote the proliferation of BSCs and inhibit them in the pre-differentiation stage. Our results further contribute to the understanding of the molecular mechanisms of carcass yield traits in beef cattle.
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Estudio de Asociación del Genoma Completo , Sitios de Carácter Cuantitativo , Bovinos/genética , Animales , Polimorfismo de Nucleótido Simple , Fenotipo , Expresión GénicaRESUMEN
Wang, Jian, Cheng-Ying Yan, Wu Wang, and Tian-Zhen Wang. Preventive effect of moderate altitude on non-culprit lesion (NCL) progression in patients with acute myocardial infarction. High Alt Med Biol. 23:345-351, 2022. Background: Ischemic postconditioning may prevent NCL progression in patients with acute myocardial infarction. Moderate altitude (1,500-2,500 m) resembles ischemic postconditioning; however, the preventive effect of moderate altitude on NCL progression is unknown. Methods: We investigated the preventive effect of moderate altitude on NCL progression in patients with ST-segment elevation myocardial infarction (STEMI) after primary percutaneous coronary intervention (PPCI). This study was an observational study. Two-hundred patients with STEMI living in Beijing, which is an average of 43.5 m above sea level (a low-altitude region), who underwent PPCI were enrolled (the control group). A further 200 patients with STEMI living in Xining, which is an average of 2,261 m above sea level (moderate-altitude region), who underwent PPCI were enrolled (the moderate-altitude group). NCL progression and related clinical factors were compared between the two groups. Results: The rate of NCL progression 12 months after PPCI in the moderate-altitude group was significantly lower compared with the control group (p < 0.01). There were 158 patients without NCL progression (group A) and 42 patients with NCL progression (group B) in the control group and 186 patients without NCL progression (group C) and 14 patients with NCL progression (group D) in the moderate-altitude group. Serum adrenaline and noradrenaline concentrations in group B were significantly higher compared with group A (p < 0.001), and serum adrenaline and noradrenaline concentrations in group D were significantly higher compared with group C (p < 0.001). Serum adrenaline, noradrenaline, and C-reactive protein concentrations in patients without NCL progression (n = 344) were significantly lower compared with patients with NCL progression (n = 56) (p < 0.01). Conclusions: Moderate altitude may prevent NCL progression. Moderate altitude may be useful for clinical rehabilitation in patients with STEMI after PPCI.
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Infarto del Miocardio , Infarto del Miocardio con Elevación del ST , Humanos , Infarto del Miocardio con Elevación del ST/terapia , Altitud , Resultado del Tratamiento , Infarto del Miocardio/prevención & control , Epinefrina , NorepinefrinaRESUMEN
Backgrounds: Growth differentiation factor 15 (GDF-15) is a highly divergent member of the TGF-ß superfamily and has been implicated in various biological functions. However, the expression of GDF-15 in patients with acute exacerbation of idiopathic pulmonary fibrosis (AE-IPF) is unclear. Method: The study included 47 AE-IPF patients, 61 stable IPF (S-IPF) subjects, and 31 healthy controls (HCs). Serum GDF-15 levels and their expression in the lung were measured. The correlation between serum GDF-15 and other clinical parameters and the risk factors for AE occurrence and the survival of IPF patients were analyzed. Results: Serum GDF-15 levels were significantly elevated in AE-IPF patients (1279.22 ± 540.02 pg/ml) as compared with HCs (891.30 ± 479.90 pg/ml) or S-IPF subjects (107.82 ± 14.21 pg/ml) (both p < 0.001). The protein and mRNA expressions of GDF-15 in the lung of AE-IPF patients were significantly increased as compared with S-IPF cases (p = 0.007 and p = 0.026, respectively). The serum GDF-15 level was correlated with the clinical variables of inflammation, metabolism, and disease severity in IPF subjects (all p < 0.05). The GDF-15 serum concentration was significantly higher in decedents than in survivors (p = 0.005). A serum GDF-15 level above 989.3 pg/ml was a risk factor for AE occurrence (p = 0.04), and the level above 1,075.76 pg/ml was an independent predictor for survival in IPF cases (p = 0.007). Conclusions: The GDF-15 level was significantly elevated in subjects with AE-IPF. GDF-15 could be a promising biomarker for AE occurrence and survival in IPF patients.
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Factor 15 de Diferenciación de Crecimiento/metabolismo , Fibrosis Pulmonar Idiopática , Biomarcadores , Factor 15 de Diferenciación de Crecimiento/genética , Humanos , Fibrosis Pulmonar Idiopática/metabolismo , Inflamación/complicaciones , Pulmón/metabolismoRESUMEN
BACKGROUND: Beef cuts in different regions of the carcass have different meat quality due to their distinct physiological function. The objective of this study was to characterize the region-specific expression differences using comparative transcriptomics analysis among five representative beef cuts (tenderloin, longissimus lumborum, rump, neck, chuck). RESULTS: We obtained 15,701 expressed genes in 30 muscle samples across five regions from carcass meat. We identified a total of 80 region-specific genes (RSGs), ranging from three (identified in the rump cut) to thirty (identified in the longissimus lumborum cut), and detected 25 transcription factors (TFs) for RSGs. Using a co-expression network analysis, we detected seven region-specific modules, including three positively correlated modules and four negatively correlated modules. We finally obtained 91 candidate genes related to meat quality, and the functional enrichment analyses showed that these genes were mainly involved in muscle fiber structure (e.g., TNNI1, TNNT1), fatty acids (e.g., SCD, LPL), amino acids (ALDH2, IVD, ACADS), ion channel binding (PHPT1, SNTA1, SUMO1, CNBP), protein processing (e.g., CDC37, GAPDH, NRBP1), as well as energy production and conversion (e.g., ATP8, COX8B, NDUFB6). Moreover, four candidate genes (ALDH2, CANX, IVD, PHPT1) were validated using RT-qPCR analyses which further supported our RNA-seq results. CONCLUSIONS: Our results provide valuable insights into understanding the transcriptome regulation of meat quality in different beef cuts, and these findings may further help to improve the selection for health-beneficial meat in beef cattle.
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Músculo Esquelético , Transcriptoma , Animales , Bovinos , Ácidos Grasos/metabolismo , Carne/análisis , Músculo Esquelético/metabolismoRESUMEN
BACKGROUND: A comprehensive analysis of gene expression profiling across tissues can provide necessary information for an in-depth understanding of their biological functions. We performed a large-scale gene expression analysis and generated a high-resolution atlas of the transcriptome in beef cattle. RESULTS: Our transcriptome atlas was generated from 135 bovine tissues in adult beef cattle, covering 51 tissue types of major organ systems (e.g., muscular system, digestive system, immune system, reproductive system). Approximately 94.76% of sequencing reads were successfully mapped to the reference genome assembly ARS-UCD1.2. We detected a total of 60,488 transcripts, and 32% of them were not reported before. We identified 2654 housekeeping genes (HKGs) and 477 tissue-specific genes (TSGs) across tissues. Using weighted gene co-expression network analysis, we obtained 24 modules with 237 hub genes (HUBGs). Functional enrichment analysis showed that HKGs mainly maintain the basic biological activities of cells, while TSGs were involved in tissue differentiation and specific physiological processes. HKGs in bovine tissues were more conserved in terms of expression pattern as compared to TSGs and HUBGs among multiple species. Finally, we obtained a subset of tissue-specific differentially expressed genes (DEGs) between beef and dairy cattle and several functional pathways, which may be involved in production and health traits. CONCLUSIONS: We generated a large-scale gene expression atlas across the major tissues in beef cattle, providing valuable information for enhancing genome assembly and annotation. HKGs, TSGs, and HUBGs further contribute to better understanding the biology and evolution of multiple tissues in cattle. DEGs between beef and dairy cattle also fill in the knowledge gaps about differential transcriptome regulation of bovine tissues underlying economically important traits.
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Ascomicetos , Perfilación de la Expresión Génica , Animales , Ascomicetos/genética , Bovinos/genética , Perfilación de la Expresión Génica/veterinaria , Fenotipo , TranscriptomaRESUMEN
BACKGROUND: Nonculprit lesions are closely related to the prognosis of patients with ST-segment elevation myocardial infarction (STEMI). Our previous research found that ischemic postconditioning (IP) could inhibit the progression of nonculprit lesions. However, the mechanism by which IP regulates the occurrence and development of nonculprit lesions remains unclear. METHODS: Firstly, a rabbit ischemia-reperfusion (IR) model was constructed. Next, the morphological characteristics of the coronary arterial tissues and myocardial tissues of the rabbits were observed using hematoxylin-eosin (H&E) staining. Then, western blot was performed to detect the expressions of AT1, Cx43, ß-tubulin, Bax, Bcl-2 and cleaved caspase 3. Finally, to further confirm the effect of IP on nonculprit coronary arterial tissues, an in vitro model of oxygen and glucose deprivation/reperfusion (OGD/R) was established. RESULTS: IR notably induced the cells apoptosis in nonculprit coronary arterial tissues and in myocardial tissues, while IR-induced cell apoptosis was significantly inhibited by IP. In addition, IP protected nonculprit coronary arterial tissues against IR via downregulating miR-92a, miR-328 and miR-494 and mRNA AT1, Cx43 and ß-tubulin. Consistently, OGD/R-induced injury of Human umbilical vein endothelial cells (HUVECs) was reversed by IP. CONCLUSIONS: In this study, IP could protect nonculprit coronary arteries against IR injury via downregulating miR-92a, miR-328 and miR-494. Our findings may provide new directions for the treatment of nonculprit lesions.
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Poscondicionamiento Isquémico , MicroARNs , Daño por Reperfusión , Animales , Apoptosis/genética , Vasos Coronarios , Células Endoteliales/metabolismo , Humanos , MicroARNs/genética , MicroARNs/metabolismo , ConejosRESUMEN
ARID3A is upregulated in colorectal cancer and can promote the proliferation and metastasis of cancer cells. However, patients with higher level of ARID3A have a better prognosis. This study aimed to uncover the mechanism by which ARID3A benefits the prognosis of colon cancer. Our results indicated that ARID3A upregulation enhanced the chemosensitivity of colon cancer cells to 5-fluorouracil (5-FU), whereas ARID3A downregulation inhibited the chemosensitivity of colon cancer cells to 5-FU. Through database analysis, we found that AKR1C3, a drug resistance-related gene, was the target of ARID3A. Moreover, AKR1C3 was downregulated in colon cancer tissues compared to normal tissues. Next, we assessed the interaction between AKR1C3 and ARID3A, and found that ARID3A inhibited the transcription of AKR1C3, leading to the downregulation of AKR1C3 in colon cancer cells. We also verified that AKR1C3 inhibited the chemosensitivity of colon cancer cells to 5-FU. Moreover, patients with higher ratio of ARID3A to AKR1C3 had a better prognosis. This study suggested that ARID3A promoted chemosensitivity of colon cancer cells by inhibiting AKR1C3 in colon cancer. The ratio of ARID3A to AKR1C3 is a good marker to predict the prognosis of colon cancer patients.
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Miembro C3 de la Familia 1 de las Aldo-Ceto Reductasas , Neoplasias del Colon , Proteínas de Unión al ADN , Factores de Transcripción , Miembro C3 de la Familia 1 de las Aldo-Ceto Reductasas/antagonistas & inhibidores , Miembro C3 de la Familia 1 de las Aldo-Ceto Reductasas/genética , Miembro C3 de la Familia 1 de las Aldo-Ceto Reductasas/metabolismo , Línea Celular Tumoral , Neoplasias del Colon/tratamiento farmacológico , Neoplasias del Colon/genética , Neoplasias del Colon/metabolismo , Neoplasias del Colon/patología , Proteínas de Unión al ADN/genética , Proteínas de Unión al ADN/metabolismo , Resistencia a Antineoplásicos , Fluorouracilo/farmacología , Humanos , Factores de Transcripción/genética , Factores de Transcripción/metabolismo , Regulación hacia ArribaRESUMEN
BACKGROUND: Epidemiological studies have confirmed that abnormal circadian rhythms are associated with tumorigenesis in breast cancer. However, few studies have investigated the pathological roles of rhythm genes in breast cancer progression. In this study, we aimed to evaluate the aberrant expression of 32 rhythm genes in breast cancer and detect the pathological roles and molecular mechanisms of the altered rhythm gene in regulating the progression of triple negative breast cancer (TNBC). METHODS: The aberrant expression of rhythm genes in breast cancer was screened by searching the GEPIA database and validated by using qRT-PCR and immunohistochemistry staining. Bioinformatics analysis combined with luciferase reporter experiment and chromatinimmunopercitation (ChIP) were used to investigate the molecular mechanism about aberrant expression of identified rhythm gene in breast cancer. The pathological roles of identified rhythm gene in TNBC progression was evaluated by colony formation assay, wound healing experiment, transwell assay, subcutaneous tumor formation and the mouse tail vein injection model through gain-of-function and loss-of-function strategies respectively. mRNA array, bioinformatics analysis, luciferase reporter experiment, ChIP and immunoflurescence assay were employed to investigate the key molecules and signaling pathways by which the identified rhythm gene regulating TNBC progression. RESULTS: We identified that nuclear factor interleukin 3 regulated (NFIL3) expression is significantly altered in TNBC compared with both normal breast tissues and other subtypes of breast cancer. We found that NFIL3 inhibits its own transcription, and thus, downregulated NFIL3 mRNA indicates high expression of NFIL3 protein in breast cancer. We demonstrated that NFIL3 promotes the proliferation and metastasis of TNBC cells in vitro and in vivo, and higher expression of NFIL3 is associated with poor prognosis of patients with TNBC. We further demonstrated that NFIL3 enhances the activity of NF-κB signaling. Mechanistically, we revealed that NFIL3 directly suppresses the transcription of NFKBIA, which blocks the activation of NF-κB and inhibits the progression of TNBC cells in vitro and in vivo. Moreover, we showed that enhancing NF-κB activity by repressing NFKBIA largely mimics the oncogenic effect of NFIL3 in TNBC, and anti-inflammatory strategies targeting NF-κB activity block the oncogenic roles of NFIL3 in TNBC. CONCLUSION: NFIL3 promotes the progression of TNBC by suppressing NFKBIA transcription and then enhancing NF-κB signaling-mediated cancer-associated inflammation. This study may provide a new target for TNBC prevention and therapy.
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Factores de Transcripción con Cremalleras de Leucina de Carácter Básico/metabolismo , Regulación Neoplásica de la Expresión Génica/genética , Inhibidor NF-kappaB alfa/metabolismo , Neoplasias de la Mama Triple Negativas/genética , Animales , Línea Celular Tumoral , Proliferación Celular , Progresión de la Enfermedad , Regulación hacia Abajo , Femenino , Humanos , Inmunohistoquímica , Ratones , Ratones Desnudos , Transducción de SeñalRESUMEN
Numerous epidemiological studies indicate that physical activity has a protective effect against colon cancer development and progression. Further, the relevant biological mechanisms where physical activity or exercise may improve survival have also been initially examined. In this review, we provide an overview of the epidemiological evidence to date which comprises 16 cohort studies of the effects of physical activity on colon cancer outcomes including cancer recurrence, cancer-specific and overall survival. Moreover, we present four potential mechanisms involving shear pressure, systemic milieu alteration, extracellular vesicles, and immune function by which physical activity and exercise may favorably impact colon cancer. Research currently in progress will provide definitive evidence of survival benefits resulting from exercise and future work will help clarify the role of targeted exercise and the relevant mechanisms involved.
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Neoplasias del Colon , Recurrencia Local de Neoplasia , Neoplasias del Colon/epidemiología , Neoplasias del Colon/prevención & control , Ejercicio Físico , HumanosRESUMEN
Beef is an important dietary source of quality animal proteins and amino acids in human nutrition. The fatty acid composition is one of the indispensable indicators affecting nutritional value of beef. However, a comprehensive understanding of the expression changes underlying fatty acid composition in representative beef cuts is needed in cattle. This study aimed to characterize the dynamics of fatty acid composition using comparative transcriptomic analysis in five different type of beef cuts. We identified 7545 differentially expressed genes (DEGs) among 10 pair-wise comparisons. Co-expression gene network analysis identified two modules, which were significantly correlated with 2 and 20 fatty acid composition, respectively. We also identified 38 candidate genes, and functional enrichment showed that these genes were involved in fatty acid biosynthetic process and degradation, PPAR, and AMPK signaling pathway. Moreover, we observed a cluster of DEGs (e.g., SCD, LPL, FABP3, and PPARD) which were involved in the regulation of lipid metabolism and adipocyte differentiation. Our results provide some valuable insights into understanding the transcriptome regulation of candidate genes on fatty acid composition of beef cuts, and our findings may facilitate the designs of genetic selection program for beneficial fatty acid composition in beef cattle.
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Marine current energy attracts much attention as a source of inexhaustible green energy. However, marine current turbines operate in a very harsh underwater environment, making it difficult to operate and maintain mechanical sensors. Therefore, the application of a sensorless control strategy is fully justified to improve the reliability of system electrical energy production. In this paper, an active disturbance rejection sensorless control strategy based on compensation sliding mode observer is proposed for the marine current turbine system. The proposed control method consists of two parts. The first part is to design an active disturbance rejection controller for the marine current turbine that will improve the system's anti-interference abilities. The second part proposes a time-delay compensation sliding mode observer based on the Smith predictor to conduct real-time delay compensation of the system. The entire system is ensured to be globally stable through the Lyapunov approach analysis. The proposed control strategy is verified by simulation, which can not only effectively suppress the lumped disturbance and eliminate the system time-delay, but also improve the power extraction capability of the system.